This KO2 application seeks support which is essential for my continued career development as a newly-independent clinical researcher. Funded by a NIDA institutional training grant, I have attained considerable expertise in the brain imaging of psychostimulant addiction over the past 4 years. I have demonstrated considerable research productivity as evidenced by my peer-reviewed publications, my scientific co-directorship of a major center, my principal- and co-investigatorships on two center sections, and a recently-awarded ROI. However this source of salary support (75%) will expire 6/31/98, leading me to seek an alternative mechanism of funding. Therefore, this KO2 award is vital for sustaining my current full- time research focus and for facilitating my maturation into a fully-independent investigator. Justification for the award is provided by a comprehensive 5-year Career Development Plan which fills important gaps in my current expertise in SPECT/PET neuroreceptor methods. Specifically, I will acquire specialized skills in several additional multidisciplinary areas: l) authorized use of radioisotopes in humans, 2) mathematical modeling and neuroreceptor quantitation, 3) digital processing and statistical analysis of imaging data, and 4) basic neurobiology of abused drugs. Intensive training is provided by an integrated curriculum of intramural coursework, extramural didactics, individualized preceptorships, interactive symposia, and research-related organizational meetings. Two representative, funded research studies are included which test two major neurochemical hypotheses of cocaine dependence in humans: sensitization and dopamine (DA) deficiency. Study #1: To establish whether cocaine addicts show a sensitized response to amphetamine as evidenced by increased displacement of the D2 radiotracer [123I]IBZM. Study #2: To determine whether cocaine addicts have reduced basal levels of DA as evidenced by smaller increases in [123I]IBZM binding following DA depletion by alpha-methyl.para-tyrosine (AMPT). These investigations illustrate the considerable impact this career award will have in furthering not only my scientific career, and also our fundamental understanding of the neurochemical mechanisms and adaptations which accompany cocaine addiction.